Analytical and clinical evaluation of the epistem genedrive assay for detection of mycobacterium tuberculosis

Shubhada Shenai, Derek T. Armstrong, Eloise Valli, David L. Dolinger, Lydia Nakiyingi, Reynaldo Dietze, Margareth Pretti Dalcolmo, Mark P. Nicol, Widaad Zemanay, Yuka Manabe, David Jamil Hadad, Patricia Marques-Rodrigues, Moises Palaci, Renata L. Peres, Mary Gaeddert, Sandra Armakovitch, Bareng A.S. Nonyane, Claudia M. Denkinger, Padmapriya Banada, Moses L. JolobaJerrold Ellner, Catharina Boehme, David Alland, Susan E. Dorman

Research output: Contribution to journalArticle

Abstract

The Epistem Genedrive assay rapidly detects the Mycobacterium tuberculosis complex from sputum and is currently available for clinical use. However, the analytical and clinical performance of this test has not been fully evaluated. The analytical limit of detection (LOD) of the Genedrive PCR amplification was tested with genomic DNA; the performance of the complete (sample processing plus amplification) system was tested by spiking M. tuberculosis mc26030 cells into distilled water and M. tuberculosis- negative sputum. Specificity was tested using common respiratory pathogens and nontuberculosis mycobacteria. A clinical evaluation enrolled adults with suspected pulmonary tuberculosis, obtained three sputum samples from each participant, and compared the accuracy of the Genedrive to that of the Xpert MTB/RIF assay using M. tuberculosis cultures as the reference standard. The Genedrive assay had an LOD of 1 pg/-l (100 genomic DNA copies/reaction). The LODs of the system were 2.5-104 CFU/ml and 2.5-105 CFU/ml for cells spiked into water and sputum, respectively. False-positive rpoB probe signals were observed in 3/32 (9.4%) of the negative controls and also in few samples containing Mycobacterium abscessus, Mycobacterium gordonae, or Mycobacterium thermoresistibile. In the clinical study, among 336 analyzed participants, the overall sensitivities for the tuberculosis case detection of Genedrive, Xpert, and smear microscopy were 45.4% (95% confidence interval [CI], 35.2% to 55.8%), 91.8% (95% CI, 84.4% to 96.4%), and 77.3% (95% CI, 67.7% to 85.2%), respectively. The sensitivities of Genedrive and Xpert for the detection of smear-microscopy-negative tuberculosis were 0% (95% CI, 0% to 15.4%) and 68.2% (95% CI, 45.1% to 86.1%), respectively. The Genedrive assay did not meet performance standards recommended by the World Health Organization for a smear microscopy replacement tuberculosis test. Epistem is working on modifications to improve the assay.

Original languageEnglish (US)
Pages (from-to)1051-1057
Number of pages7
JournalJournal of clinical microbiology
Volume54
Issue number4
DOIs
StatePublished - Apr 2016

ASJC Scopus subject areas

  • Microbiology (medical)

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    Shenai, S., Armstrong, D. T., Valli, E., Dolinger, D. L., Nakiyingi, L., Dietze, R., Dalcolmo, M. P., Nicol, M. P., Zemanay, W., Manabe, Y., Hadad, D. J., Marques-Rodrigues, P., Palaci, M., Peres, R. L., Gaeddert, M., Armakovitch, S., Nonyane, B. A. S., Denkinger, C. M., Banada, P., ... Dorman, S. E. (2016). Analytical and clinical evaluation of the epistem genedrive assay for detection of mycobacterium tuberculosis. Journal of clinical microbiology, 54(4), 1051-1057. https://doi.org/10.1128/JCM.02847-15